W Poon1, C Matula2, P E Vos3, D F Muresanu4,5, N von Steinbüchel6, K von Wild7, V Hömberg8, E Wang9, T M C Lee10, S Strilciuc11,12, J C Vester13. 1. Division of Neurosurgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China. 2. Department of Neurosurgery, Medical University of Vienna, Vienna, Austria. 3. Department of Neurology, Slingeland Hospital, Doetinchem, The Netherlands. 4. Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania. dafinm@ssnn.ro. 5. RoNeuro Institute for Neurological Research and Diagnostic, No. 37 Mircea Eliade Street, 400364, Cluj-Napoca, Romania. dafinm@ssnn.ro. 6. Institute of Medical Psychology and Medical Sociology, University Medical Centre Göttingen, Göttingen, Germany. 7. Medical Faculty, Westphalia Wilhelm's University, Münster, Germany. 8. Department of Neurology, SRH Gesundheitszentrum Bad Wimpfen GmbH, Bad Wimpfen, Germany. 9. Department of Neurosurgery, National Neuroscience Institute, Singapore, Singapore. 10. State Key Laboratory of Brain and Cognitive Sciences and Laboratory of Neuropsychology, The University of Hong Kong, Pokfulam, Hong Kong, China. 11. Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania. 12. RoNeuro Institute for Neurological Research and Diagnostic, No. 37 Mircea Eliade Street, 400364, Cluj-Napoca, Romania. 13. Department of Biometry and Clinical Research, idv Data Analysis and Study Planning, Krailling, Germany.
Abstract
OBJECTIVE: To evaluate the safety and efficacy of Cerebrolysin as an add-on therapy to local standard treatment protocol in patients after moderate-to-severe traumatic brain injury. METHODS: The patients received the study medication in addition to standard care (50 mL of Cerebrolysin or physiological saline solution daily for 10 days, followed by two additional treatment cycles with 10 mL daily for 10 days) in a prospective, randomized, double-blind, placebo-controlled, parallel-group, multi-centre phase IIIb/IV trial. The primary endpoint was a multidimensional ensemble of 14 outcome scales pooled to be analyzed by means of the multivariate, correlation-sensitive Wei-Lachin procedure. RESULTS: In 46 enrolled TBI patients (Cerebrolysin 22, placebo 24), three single outcomes showed stand-alone statistically significant superiority of Cerebrolysin [Stroop Word/Dots Interference (p = 0.0415, Mann-Whitney(MW) = 0.6816, 95% CI 0.51-0.86); Color Trails Tests 1 and 2 (p = 0.0223/0.0170, MW = 0.72/0.73, 95% CI 0.53-0.90/0.54-0.91), both effect sizes lying above the benchmark for "large" superiority (MW > 0.71)]. While for the primary multivariate ensemble, statistical significance was just missed in the intention-to-treat population (pWei-Lachin < 0.1, MWcombined = 0.63, 95% CI 0.48-0.77, derived standardized mean difference (SMD) 0.45, 95% CI -0.07 to 1.04, derived OR 2.1, 95% CI 0.89-5.95), the per-protocol analysis showed a statistical significant superiority of Cerebrolysin (pWei-Lachin = 0.0240, MWcombined = 0.69, 95% CI 0.53 to 0.85, derived SMD 0.69, 95% CI 0.09 to 1.47, derived OR 3.2, 95% CI 1.16 to 12.8), with effect sizes of six single outcomes lying above the benchmark for "large" superiority. Safety aspects were comparable to placebo. CONCLUSION: Our trial suggests beneficial effects of Cerebrolysin on outcome after TBI. Results should be confirmed by a larger RCT with a comparable multidimensional approach.
RCT Entities:
OBJECTIVE: To evaluate the safety and efficacy of Cerebrolysin as an add-on therapy to local standard treatment protocol in patients after moderate-to-severe traumatic brain injury. METHODS: The patients received the study medication in addition to standard care (50 mL of Cerebrolysin or physiological saline solution daily for 10 days, followed by two additional treatment cycles with 10 mL daily for 10 days) in a prospective, randomized, double-blind, placebo-controlled, parallel-group, multi-centre phase IIIb/IV trial. The primary endpoint was a multidimensional ensemble of 14 outcome scales pooled to be analyzed by means of the multivariate, correlation-sensitive Wei-Lachin procedure. RESULTS: In 46 enrolled TBI patients (Cerebrolysin 22, placebo 24), three single outcomes showed stand-alone statistically significant superiority of Cerebrolysin [Stroop Word/Dots Interference (p = 0.0415, Mann-Whitney(MW) = 0.6816, 95% CI 0.51-0.86); Color Trails Tests 1 and 2 (p = 0.0223/0.0170, MW = 0.72/0.73, 95% CI 0.53-0.90/0.54-0.91), both effect sizes lying above the benchmark for "large" superiority (MW > 0.71)]. While for the primary multivariate ensemble, statistical significance was just missed in the intention-to-treat population (pWei-Lachin < 0.1, MWcombined = 0.63, 95% CI 0.48-0.77, derived standardized mean difference (SMD) 0.45, 95% CI -0.07 to 1.04, derived OR 2.1, 95% CI 0.89-5.95), the per-protocol analysis showed a statistical significant superiority of Cerebrolysin (pWei-Lachin = 0.0240, MWcombined = 0.69, 95% CI 0.53 to 0.85, derived SMD 0.69, 95% CI 0.09 to 1.47, derived OR 3.2, 95% CI 1.16 to 12.8), with effect sizes of six single outcomes lying above the benchmark for "large" superiority. Safety aspects were comparable to placebo. CONCLUSION: Our trial suggests beneficial effects of Cerebrolysin on outcome after TBI. Results should be confirmed by a larger RCT with a comparable multidimensional approach.
Authors: Maria Cristina Morganti-Kossmann; Mario Rancan; Philip F Stahel; Thomas Kossmann Journal: Curr Opin Crit Care Date: 2002-04 Impact factor: 3.687
Authors: Peter Y M Woo; Joanna W K Ho; Natalie M W Ko; Ronald P T Li; Leo Jian; Alberto C H Chu; Marco C L Kwan; Yung Chan; Alain K S Wong; Hoi-Tung Wong; Kwong-Yau Chan; John C K Kwok Journal: BMC Neurol Date: 2020-11-03 Impact factor: 2.474